1. Field of the Invention
This invention relates to a sealing stopper for a syringe and a prefilled syringe consisting of an injection cylinder or two-component cylinder in which a medicament is sealed by the use of the sealing stopper for a syringe.
2. Description of the Prior Art
An injection agent as one agent form of a medicament includes a solid formulation to be dissolved in administering and a liquid formulation prepared in the form of a solution. As a means for administering an injection agent in the body, there are a method comprising directly administering a medicament liquid in the body from a syringe and a method comprising mixing an injection agent with another medicament liquid held by another container just before administering and then introducing the mixture into the body through an administering system, for example, another medical instrument than syringes, such as drip injection set.
In the so-called prefilled syringe, an injection agent is previously filled in an injection cylinder-cum-container, transported or kept in custody, while sealing the end thereof by a sealing stopper. For the adminisration of the injection agent, an injection needle or administration device is fitted to the pointed end, after which the sealing stopper is thrust toward the pointed end and slidably moved to allow the injection agent to flow out of the injection needle side and administer it. This syringe of prefilled type has various advantages that 1 operation thereof is very simple, 2 administration of a medicament is feasible with a correct administration quantity without misuse of a medicament even in case of emergency and 3 removal of a medicament is not required to prevent the medicament from contamination with microorganisms and to maintain highly sanitary conditions. Thus, the syringe of prefilled type has lately been used often so as to improve the efficiency of medical treatment in the actual medical scene and to prevent contamination with microorganisms. Further, it has been recommended to use a so-called kit article consisting of a system of a solid agent, water for dissolving the solid agent and a medicament liquid, in combination, because of the same reason.
Such a prefilled syringe is convenient as described above, but when a medicament is kept in custody, high sealing property is required and simultaneously, slidable movement of a sealing stopper is required in administering. Namely, the prefilled syringe must have a function of opposite properties, that is, sealing property and slidable property.
In syringes of the prior art, silicone oils have been coated onto a piston to unite both the sealing property and slidable property. Of late, however, there arise problems, for example, lowering of the potency due to adsorption of effective components of a medicament on the silicone oil, contamination of a medicament with fine grains as a stripped product of a silicone oil and bad influences upon the human body thereby (poisonous character of silicone oil). Accordingly, there is a late tendency of avoiding use of silicone oils.
On the other hand, a movable sealing rubber stopper (which will hereinafter be referred to as "sealing stopper" in some cases) whose main body consists of a rubber has hitherto been known. Examples include one having a fluoro resin film such as tetrafluoroethylene laminated on the surface to be contacted with a medicament liquid (Japanese Utility Model Publication No. 8990/1973), a sealing rubber stopper for and a prefilled syringe having a polypropylene resin film laminated on all sites to be contacted with an inner surface of a syringe (U.S. Pat. No. 4,554,125), etc.
Under the situation, the inventors have developed and proposed syringes or two-component syringes capable of satisfying both the sealing property and slidable property without using silicone oils and having high sanitary and safety property. Examples include a sealing stopper whose surface is coated with a tetrafluoroethylene-ethylene copolymer resin (which will hereinafter be referred to as "ETFE" in some cases), as disclosed in Japanese Patent Laid-Open Publication No. 139668/1987, a sealing stopper whose surface is coated with a polytetrafluoroethylene resin film (which will hereinafter be referred to as "PTFE" in some cases), as disclosed in Japanese Patent Laid-Open Publication No. 97173/1988, and a sealing stopper laminated with PTFE, ETFE or ultrahigh molecular polyethylene resin film having a shape suitable for a prefilled syringe, as disclosed in Japanese Utility Model Laid-Open Publication No. 138454/1989 or 138455/1989. Furthermore, there has been proposed a syringe consisting of a cyclic olefin plastic capable of satisfying both the sealing property and slidable property in combination with the sealing stopper as described above, as disclosed in Japanese Patent Laid-Open Publication No. 293159/1993.
In the general formulation provisions of the Japanese Pharmacopoeia of 13th Revision, it is provided that a container for an injection agent must be a hermetic container and the hermetic container is defined as a container capable of daily handling and preventing a medicament from being contaminated with gases or microorganisms during ordinary storage. Considering the prior art in view of this official provision, the resin film-laminated sealing stopper has a large effect on inhibition of dissolving-out of a rubber component of the stopper body, but the sealing property tends to be lowered because of not using silicone oil.
In the above described sealing stopper the inventors have developed, it is necessary in order to maintain a sufficientsealing property to design so that a difference between the outer diameter of the sealing stopper and the inner diameter of the syringe is somewhat large. Consequently, there arises a problem that the sliding resistance during administering a medicament is somewhat increased.
On the other hand, the inventors have made various studies about resins to be laminated on surfaces of sealing stoppers and consequently, have reached a conclusion that PTFE is most suitable, and that high molecular weight polyethylene (which will hereinafter be referred to as "UHMWPE" some times) is preferably used in addition to fluoro resins, as compared with other fluoro resins. Examples include tetrafluoroethylene-perfluoroethylenc copolymer (PFA), tetrafluoroethylenene-hexafluoropropylene copolymer (FEP), tetrafluoroethylene-ethylene copolymer (ETFE), trichlorotrifluoroethylene (PCTFE), polyvinylidene fluoride (PVDF), polyvinyl fluoride (PVF), etc. The reasons therefor will be illustrated below.
The above described other fluoro resins can be subjected to thermal melt molding, for example, injection molding or extrusion molding, but PTFE having a melt flow rate (MFR) of substantially zero at its melting point of 327.degree. C. and being non-sticky cannot be subjected to thermal melt molding [Cf. "Plastic No Jiten (Plastic Dictionary)", page 836-838, published by Asakura Shoten, Mar. 1, 1992]. Accordingly, a film of PTFE is obtained by compression molding to give a sheet, by shaping in a block and cutting or slicing the block to give a relatively thick sheet or by skiving working to give a thinner film.
The skiving method will further be illustrated in detail. A suitable amount of a powdered resin raw material for shaping working, obtained by suspension polymerization to give a grain diameter of .about.10 .mu.m, is charged in a metallic mold for sintering shaping, previously shaped at room temperature and at a pressure of 100 to 1000 kg/cm.sup.2 in a compression press and then sintered at 360 to 380.degree. C. for several hours ordinarily but depending on the size of a shaped product. Then, the metallic mold is cooled at normal pressure or at some pressure, thus obtaining a primary shaped product in the form of a sheet, block or cylinder. The shaped product of PTFE in the form of a cylinder, obtained in the above described compression shaping, is fitted to a lathe and revolved, during which an edged tool is pressed against the shaped product at a constant pressure and a specified angle to obtain a PTFE film with a thickness of 40 to 50 .mu.m and at most 200 .mu.m.
The film prepared by this skiving method has a disadvantage that there remain pinholes or skiving scratches on the surface thereof and accordingly, the film is not suitable for laminating a sealing stopper for preventing it from leaching of rubber components in a medicament and contaminating the medicament.
On the other hand, a casting method comprising adding a latex emulsion to a suspension of fine grains of a fluoro resin, thinnly spreading the mixture on a metallic surface and then burning to obtain a film has been known as disclosed in U.S. Pat. No. 5,194,335. According to this method, a film with a thickness of up to about 3 .mu.m can be produced.